Compositions and Methods for Injectable Composition for an Accommodating Intraocular Lens

ABSTRACT

The present disclosure relates to injectable compositions and methods of making injectable compositions of moisture curing siloxane polymers for forming accommodating intraocular lenses. In certain embodiments, the moisture curing siloxane polymers are comprised of an organosilicon compound and a hydrolytically sensitive siloxane moiety and have a specific gravity of greater than about 0.95, a number average molecular weight (M n ) greater than about 5,000 or about 20,000 and a weight average molecular weight (M w ) greater than about 20,000 or about 40,000. The disclosure includes accommodating intraocular lenses formed from moisture curing siloxane polymers and having a modulus of elasticity of less than about 6 kPa, less than 20% post-cure extractables, refractive index ranging from 1.4 to 1.5 and dioptric range of accommodation of 0D to 10D.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/535,671, filed Jun. 13, 2017, which is the National Phase applicationof International Application No. PCT/AU2015/050821, filed Dec. 21, 2015,which designates the United States and was published in English, whichclaims the benefit of U.S. Provisional Application No. 62/095,387, filedDec. 22, 2014. The entire contents of each of these applications areincorporated herein by reference.

This application is also related to U.S. Pat. No. 7,001,426 entitled“One-Piece Minicapsulorhexis Valve” and U.S. Pat. No. 6,358,279 entitled“Minicapsulorhexis Valve.” Each of these patents are incorporated hereinby reference in their entirety.

FIELD

The present disclosure relates to compositions using moisture curingsiloxane polymers for forming accommodating intraocular lenses, forexample, in situ. The disclosure also relates to compositions and/ormethods of making injectable compositions for forming accommodatingintraocular lenses using moisture curing siloxane polymers as well asmethods of forming accommodating intraocular lenses, for example, insitu (in the eye of a warm blooded animal).

BACKGROUND

Accommodation is the ability of the eye to change the power of the eyeto enable clear vision with objects in focus for a range of distances.With a change in focus from distance to near vision, the ciliary musclecontracts, the zonules (filaments that connect the crystalline lens tothe ciliary muscle) relax and the crystalline lens takes a more roundedform resulting in an increase in power and resulting in the ability ofthe eye to focus on near objects. However, with age, there is a gradualdecline in the accommodative power of the eye due to the crystallinelens losing its flexibility in changing its shape and in humans, intheir forties this results in blurred vision for near tasks such asreading and is called Presbyopia. The condition is commonly managed withglasses or contact lenses.

In those that have cataracts, the crystalline lens is extracted and anintraocular lens is commonly implanted. Typically, the intraocular lensis a fixed focus lens that enables the eye to see distant objects. Sincethe implanted lens is unable to change shape and thus a change in power,the condition typically necessitates the use of spectacle lenses to beable to see at near. In both these situations, i.e. in presbyopia andfollowing cataract extraction, the desire is to eliminate or reduce theneed for spectacles for near distances and restore the accommodativepower i.e. the re-establishment of the eye's ability to focus for arange of distances.

While many approaches have been explored, the development of a flexiblematerial that would replace the natural material of the crystalline lensand fill the capsular bag and provide accommodation is highly desired.For example, two part silicone elastomers (referred to as RTV or LTVsilicones) require a polyfunctional vinyl siloxane as one component anda polyfunctional hydrosiloxane silicone polymer as the other componentand cure at body temperature via platinum catalysed hydrosilationreaction. However, these compositions suffer from the need to mix thetwo polymers immediately prior to injection and introduced into thecapsular bag before the viscosity of the composition rises too far.Another approach is based on use of compositions of polysiloxanes withphotocurable moieties, however it has been said that the modulus of thecured composition is too high to restore accommodation. Another approachinvolves hydrogel compositions that offer access to low moduluscompositions but involve UV curing that poses a problem with respect totheir safety for surrounding tissues. Also the resultant curedcomposition did not achieve the desired refractive index to provide forthe accommodative power and also suffered from post cure swelling.

Thus there is a continued demand for compositions and methods that aredisclosed herein. For example, compositions suitable for injection intothe capsular bag of the eye of a warm blooded animal and are able to becured in situ and allow for restoration of accommodative power.

Reference to prior art in this specification is not, and should not betaken as acknowledgement or form of suggestion that this prior art formspart of the general knowledge in Australia or other jurisdictions orthat this prior art could reasonably be expected to be ascertained,understood and regarded as relevant by person skilled in the art.

SUMMARY

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietyto form an accommodating intraocular lens in situ in the capsular bag ofan eye of a warm blooded animal (for example, a human patient). Certainembodiments are directed to an injectable composition comprising anorganosilicon compound and a hydrolytically sensitive siloxane moiety toform an accommodating intraocular lens for use in an eye of a humanpatient. Certain embodiments are directed to an injectable compositioncomprising an organosilicon compound and a hydrolytically sensitivesiloxane moiety that when introduced into the capsular bag of an eye ofa warm blooded animal, the composition substantially cures in situ uponcontact with one or more of the following: moisture, water and/or anaqueous medium to form an accommodating intraocular lens. The result isa substantially cured composition that forms an intraocular lens that issuitably transparent and a refractive index that is suitably close to orgreater than that of a natural crystalline lens. Moreover, thesubstantially cured composition may have a modulus of elasticity in arange that may be capable of deforming with the stretching and relaxingforces on the capsular bag from the ciliary muscle via the zonules. Thedeformation of the intraocular lens may result in a change of the powerof the eye and thus accommodation.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95 and the injectablecomposition is substantially cured in situ upon contact with moisture,water and/or an aqueous medium to form an accommodating intraocularlens. In certain embodiments, the organosilicon compound compriseslinear polysiloxane polymer chains, polysiloxane copolymer chains,branched polysiloxane polymer chains, or combinations thereof. Incertain embodiments, the hydrolytically sensitive siloxane moietycomprises one or more silane ether and silane ester groups. In certainembodiments, the specific gravity of the composition prior to curingwould typically be sufficient to enable filling of the capsular bagwithout the composition floating on top of the aqueous medium. Incertain embodiments, the specific gravity is about 0.96 to 1.06. Inother embodiments, the specific gravity is 0.97 to 1.05, 0.98 to 1.05,0.99 to 1.05, 1 to 1.04, 1 to 1.05, 1.1 to 1.5, about 1.2 to 1.5 orabout 1.3 to 1.5.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n)) of the injectable composition is greater thanabout 20,000 and the injectable composition is substantially cured insitu upon contact with moisture, water and/or an aqueous medium to forman accommodating intraocular lens.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n)) of the injectable composition is greater thanabout 5,000, and the injectable composition is substantially cured insitu upon contact with moisture, water and/or an aqueous medium to forman accommodating intraocular lens.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n)) of the injectable composition is greater thanabout 20,000, the weight average molecular weight (M_(w)) of theinjectable composition is greater than about 40,000 and the injectablecomposition is substantially cured in situ upon contact with moisture,water and/or an aqueous medium to form an accommodating intraocularlens.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n)) of the injectable composition is greater thanabout 5,000, the weight average molecular weight (M_(w)) of theinjectable composition is greater than about 20,000 and the injectablecomposition is substantially cured in situ upon contact with moisture,water and/or an aqueous medium to form an accommodating intraocularlens.

In other embodiments, the M_(n) of the injectable composition is 20,000to 150,000, 20,000 to 140,000, 20,000 to 120,000, 20,000 to 100,000,20,000 to 80,000, 20,000 to 60,000, 20,000 to 40,000, 5,000 to 20,000 or5,000 to 10,000. In other embodiments, the M_(n) of the injectablecomposition is at least about 5,000, at least about 10,000, at leastabout 20,000, at least about 40,000, at least about 60,000, at leastabout 80,000 or at least about 100,000. In other embodiments, the weightaverage molecular weight (M_(w)) of the injectable composition isgreater than about 40,000. In certain embodiments, the weight averagemolecular weight (M_(w)) of the injectable composition is between about40,000 to about 300,000, about 40,000 to about 250,000, about 40,000 toabout 200,000, about 40,000 to about 150,000, about 40,000 to about100,000, 20,000 to about 50,000. In certain embodiments, the weightaverage molecular weight (M_(w)) of the injectable composition is atleast 20,000, at least about 40,000, at least about 80,000, at leastabout 120,000, at least about 160,000, at least about 200,000, at leastabout 240,000 and at least about 280,000. In other embodiments, theM_(n) of the injectable composition is 5,000 to 150,000, 5,000 to140,000, 5,000 to 120,000, 5,000 to 100,000, 5,000 to 80,000, 5,000 to60,000 or 5,000 to 40,000. In other embodiments, the weight averagemolecular weight (M_(w)) of the injectable composition is greater thanabout 20,000. In certain embodiments, the weight average molecularweight (M_(w)) of the injectable composition is between about 20,000 toabout 300,000, about 20,000 to about 250,000, about 20,000 to about200,000, about 20,000 to about 150,000 or about 20,000 to about 100,000.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a viscosity suitable for injection through an injection device. Incertain embodiments, the viscosity of the injectable composition is atleast about 0.5 Pa·s. In other embodiments, the viscosity of theinjectable composition is between about 0.5 to 30 Pa·s, 0.5 to 25 Pa·s,0.5 to 20 Pa·s, 0.5 to 15 Pa·s, 0.5 to 10 Pa·s and 0.5 to 5 Pa·s.Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n))) between 20,000 to 150,000, the weight averagemolecular weight (M_(w)) between 40,000 to 300,000, viscosity of about0.5 to 30 Pa·s and is substantially cured in situ upon contact withmoisture, water and/or an aqueous medium to form an accommodatingintraocular lens.

Certain embodiments are directed to an injectable composition comprisingan organosilicon compound and a hydrolytically sensitive siloxane moietywith a specific gravity greater than about 0.95, the number averagemolecular weight (M_(n)) between 5,000 to 150,000, the weight averagemolecular weight (M_(w)) between 20,000 to 300,000, viscosity of about0.5 to 30 Pa·s and is substantially cured in situ upon contact withmoisture, water and/or an aqueous medium to form an accommodatingintraocular lens.

In certain embodiments, to obtain a substantially cured composition, themole fraction of the end groups that possess a hydrolysable and crosslinkable moiety is between about 20% to about 100%. In otherembodiments, the mole fraction of the end groups that possess ahydrolysable and cross linkable moiety of the injectable composition isat least about 20%. In other embodiments, the mole fraction of the endgroups that possess a hydrolysable and cross linkable moiety of theinjectable composition is between 20% to 95%, 20% to 90%, 20% to 85%,20% to 80%, 20% to 75%, 20% to 70% and 20% to 65%, 20% to 60%, 20% to55%, 20% to 50%, 20% to 45%, 20% to 40%, 20% to 35%, 20% to 30% and 20%to 25%. In other embodiments, the mole fraction of the end groups thatpossess a hydrolysable and cross linkable moiety of the injectablecomposition is at least about 95%, about 90%, about 85%, about 80%,about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about45%, about 40%, about 35%, about 30%, about 25% and about 20%.

Certain embodiments are to a method of making an injectable compositionfor forming an accommodating intraocular lens in situ, comprising thestep of mixing together an organosilicon compound and a hydrolyticallysensitive siloxane moiety using catalytic hydrosilylation orcondensation reaction to form a one-part injectable composition. Incertain embodiments, the organosilicon compound may comprise linearpolysiloxane polymer chains, polysiloxane copolymer chains, branchedpolysiloxane polymer chains, or combinations thereof. In certainembodiments, the organosilicon compound may include hydride terminatedpolydimethylsiloxane polymer chains or vinyl terminatedpolydimethylsiloxane polymer chains. In other embodiments, theorganosilicon compound may include polyphenyl-methyl siloxane orpolydiphenylsiloxane. In other embodiments, the hydrolytically sensitivesiloxane moiety may comprise one or more of silyl ester groups or one ofmore silyl ether groups. In other embodiments, the hydrolyticallysensitive siloxane moiety may include one or more of the following: forhydride terminated polymer chains: diethoxymethylvinylsilane,methyldiethoxyvinylsilane, triethoxyvinylsi lane,dimethyldimethoxysilane, vinyldiacetoxymethylsilane,vinyldimethylacetoxysilane and allytriethoxysilane; for vinyl terminatedpolymer chains: diethoxymethylsilane, diacetoxymethylsilane,dimethylethoxysilane, dimethylacetoxysilane and triethoxysilane. Thecompounds may be synthesised by using methods that are known or obtainedcommercially for example from Gelest, Inc (PA, USA). In certainembodiments, the catalytic hydrosilation may be performed using one ormore of catalysts including chloroplatinic acid, Karstedt's catalyst,Palladium acetate and Platinum Oxide. In certain embodiments where thehydrolytically sensitive siloxane moiety may be introduced through acondensation reaction, polymer macromonomers with silanol end groups maybe condensed with polyfunctional silyl ester and silyl ether monomerssuch as tetraethylorthosilicate, methyltrimethoxysilane ormethyltriacetoxysilane.

Certain embodiments relate to an accommodating intraocular lens formedin situ in the eye of a warm blooded animal by injecting a compositioncomprising an organosilicon compound and a hydrolytically sensitivesiloxane moiety into the capsular bag of the eye of a warm bloodedanimal and allowing the composition to cure substantially upon contactwith moisture, water or an aqueous medium to form the intraocular lens.The accommodating intraocular lens formed in situ may have certainproperties or combination of properties. In certain embodiments, to beable to change shape and thus power and accommodative power of the eye,the modulus of the substantially cured composition is at least 6 kPa. Inother embodiments, the modulus of elasticity is between 0.1 to 6 kPa,0.1 to 5 kPa, 0.1 to 4 kPa, 0.1 to 3 kPa, 0.1 to 2 kPa, 2 to 6 kPa, 2 to5 kPa, 2 to 4 kPa, 2 to 3 kPa, at least 2 kPa or at least 0.1 to 2 kPa.

In certain embodiments, the refractive index of the substantially curedcomposition ranges from about 1.4 to about 1.5. In certain embodiments,the refractive index is at least 1.4. To obtain the substantially curedcomposition with the desired refractive index, the proportion of theorganosilicon compound and the hydrolytically sensitive siloxane moietymay be varied. In certain embodiments, the organosilicon compound mayinclude polyphenyl-methyl siloxane or polydiphenylsiloxane to have arefractive index greater than about 1.41. In other embodiments, therefractive index is between 1.4 to 1.5, 1.4 to 1.48, 1.4 to 1.46, 1.4 to1.44, 1.4 to 1.43, 1.4 to 1.42, 1.42 to 1.44, at least 1.41 or at least1.42.

In certain embodiments, the extractables from the substantially curedcomposition is less than about 20%. In other embodiments, theextractables from the substantially cured composition is from about 0.5%to about 15% or about 0.5% to about 10%. In the other embodiments, theextractables from the substantially cured composition is between 0.5 to20%, 0.5 to 18%, 0.5 to 16%, 0.5 to 14%, 0.5 to 12% 0.5 to 10%, 0.5 to8%, 0.5 to 7%, 0.5% to 6%, 0.5 to 5%, 1 to 4%, 1 to 5%, 1 to 7%, 1 to8%, 1 to 10%, 1 to 12%, 1 to 14%, 1 to 16%, 1 to 18%, less than 20%,less than 15%, less than 12%, less than 10%, less than 8%, less than 6%,less than 4% or less than 2%. In certain embodiments, at least 50% theextractables from the substantially cured composition have numberaverage molecular weight (M_(n)) greater than about 30,000. In certainembodiments, at least 50% of the extractables from the substantiallycured composition have number average molecular weight (M_(n)) greaterthan about 10,000. In other embodiments, the percent of extractablesfrom the cured composition with M_(n) greater than 30,000 is at least 30to 55%, 35 to 55%, 40 to 55%, 45 to 55%, at least 55% or at least 45%.In other embodiments, the percent of extractables from the curedcomposition with M_(n) greater than 10,000 is at least 30 to 55%, 35 to55%, 40 to 55%, 45 to 55%, at least 55% or at least 45%. In certainembodiments, at least 50% of the extractables from the substantiallycured composition have number average molecular weight (M_(n)) greaterthan 10,000, greater than 20,000, greater than 25,000 or greater than35,000. In other embodiments, the substantially cured composition has adioptric range of accommodation of 0.5 D to 10 D, 0.5 D to 8 D, 0.5 D to6 D, 0.5 D to 5 D, 0.5 D to 4 D, 0.5 D to 3D, 1 D to 2 D, at least 1 D,at least 2D, at least 3D or at least 4 D. In other embodiments, thesubstantially cured composition has a dioptric range of accommodation of0 D to 10 D, 0 D to 8 D, 0 D to 6 D, 0 D to 5 D, 0 D to 4 D, 0 D to 3D,0 D to 2D, 0 D to 1 D, up to 1 D, up to 2D, up to 3D, up to 4 D, up to 5D, up to 6 D, up to 7 D, up to 8 D, up to 9 D and up to 10 D. Thedioptric range of accommodation of the substantially cured compositionmay be measured using suitable techniques, such as the Ex VivoAccommodation Simulator (EVAS). In certain embodiments, thesubstantially cured composition is suitably transparent. In certainembodiments, the substantially cured composition permits about 80% ormore of visible light to be transmitted. In other embodiments, the rangeof visible light that is transmitted ranges from about 80% to about 95%,80% to 90%, 80% to 85% or at least 80%. In other embodiments, suitablytransparent may mean that at least 80%, 85%, 90%, 95% or 98% of thevisible light is capable of being transmitted through the substantiallycured or cured composition. The visible light transmission of thesubstantially cured composition may be measured using suitabletechniques, such as the spectrometer.

Certain embodiments relate to an intraocular lens comprising a polymerwith an organosilicon compound and hydrolytically sensitive siloxanemoiety and having one or more properties of an elastic modulus of 6 kPaor less; less than 20% of post-cure extractables. Other embodimentsrelate to an accommodating intraocular lens comprising a polymer with anorganosilicon compound and hydrolytically sensitive siloxane moiety andhaving one or more properties of an elastic modulus of 6 kPa or less;less than 20% of post-cure extractables with at least 50% of theextractables having M_(n) greater than about 30,000. Other embodimentsrelate to an accommodating intraocular lens comprising a polymer with anorganosilicon compound and hydrolytically sensitive siloxane moiety andhaving one or more properties of an elastic modulus of 6 kPa or less;less than 20% of post-cure extractables with at least 50% of theextractables having M_(n) greater than about 30,000 and a refractiveindex in range of about 1.4 to about 1.5.

Certain other embodiments relate to an accommodating intraocular lenscomprising an organosilicon compound and hydrolytically sensitivesiloxane moiety polymer and having one or more properties of an elasticmodulus of 6 kPa or less, less than 20% of post-cure extractables, atleast 50% of the extractables having M_(n) greater than about 30,000, arefractive index in the range of about 1.4 to about 1.5 and a dioptricrange of accommodation of 0.5 D to 10 D. Certain other embodimentsrelate to an accommodating intraocular lens comprising an organosiliconcompound and hydrolytically sensitive siloxane moiety polymer and havingone or more properties of an elastic modulus of 6 kPa or less, less than20% of post-cure extractables, at least 50% of the extractables havingM_(n) greater than about 30,000, a refractive index in the range ofabout 1.4 to about 1.5 and a dioptric range of accommodation of 0 D to10 D.

The present disclosure further relates to a kit comprising one or moreof a) injectable composition comprising an organosilicon compound and ahydrolytically sensitive siloxane moiety and having a specific gravitygreater than 0.95 b) an injection device and/or c) a valve device. Theinjection device may be prefilled with the injectable composition or theinjectable composition may be available for refilling into the device ata later stage. The injection device may consist of a syringe and acannula. The syringe and cannula may be designed to support manualinjection of the composition into the capsular bag of an eye of apatient without undue force. The cannula may be designed to becompatible with a small capsulorrhexis of the capsular bag. The cannulamay be capped with a protective sleeve.

The injectable composition is typically delivered using the injectiondevice as described herein into the capsular bag of the eye of a warmblooded animal through a small aperture created with an incision orcapsulorrhexis of the anterior capsular surface of the eye. Leakage ofthe injected composition from the capsular bag into the surroundingsthrough the small incision or capsulorrhexis is undesirable. Thus thekit may further comprise a valve device which may be used to seal orplug or close or approximate the aperture on the capsular surfacepreventing leakage of the composition from the capsular bag of the eye.The valve may be an one-piece minicapsulorrhexis valve for example, asdescribed in U.S. Pat. No. 7,001,426 and/or 6,358,279 or a similardevice and may be used at one or more of the following phases: prior tofilling, during filling and after filling of the capsular bag of the eyeof a warm blooded animal to prevent, or substantially prevent, leakageof the composition.

The present disclosure is directed, at least in part, to compositionsthat have one or more of the following characteristics and/oradvantages:

-   -   the composition prior to cure has a viscosity range such that it        is injectable;    -   the injectable composition on visual inspection is colourless,        substantially colourless or sufficiently colourless;    -   the injectable composition is transparent, substantially        transparent, suitably transparent or sufficiently transparent;    -   the injectable composition is safe for use in situ in an eye of        a warm blooded animal due at least in part to the moisture cure        mechanism;    -   the cured composition is safe for use in situ in an eye of a        warm blooded animal due at least in part to the moisture cure        mechanism    -   the cured composition is transparent, substantially transparent,        suitably transparent or sufficiently transparent;    -   the cured composition is sufficiently able to change shape due        at least in part to the modulus of the cured composition;    -   the cured composition has a refractive index that is close, or        suitably close to the refractive index of the crystalline lens        of the eye of the warm blooded animal;    -   the cured composition is able to achieve a sufficient dioptric        range of accommodation.

DETAILED DESCRIPTION

The present disclosure is described in further detail with reference toone or more embodiments. The examples and embodiments are provided byway of explanation and are not to be taken as limiting to the scope ofthe disclosure.

The term “comprise” and its derivatives (e.g., comprises, comprising) asused in this specification is to be taken to be inclusive of features towhich it refers, and is not meant to exclude the presence of additionalfeatures unless otherwise stated or implied.

The features disclosed in this specification (including accompanyingclaims and abstract) may be replaced by alternative features serving thesame, equivalent or similar purpose, unless expressly stated otherwise.

In the context of this specification, the terms “a” and “an” are usedherein to refer to one or to more than one (i.e. to at least one) of thegrammatical object of the article. By way of example, “an element” meansone element or more than one element.

The subject headings used in the detailed description are included forthe ease of reference of the reader and should not be used to limit thesubject matter found throughout the disclosure or the claims. Thesubject headings should not be used in construing the scope of theclaims or the claim limitations.

As used herein, the term “organosilicon compound” is understood to referto compounds that contain silicon-carbon bonds in their molecules suchas polydimethylsiloxanes.

As used herein, the term “hydrolytically sensitive siloxane moiety” isunderstood to refer to a siloxane or silyl substituent that, upon cominginto contact with moisture, or water and/or an aqueous medium undergoesa reaction with the water molecule to liberate a small condensationproduct and leave a reactive silanol in its place.

As used herein, in certain embodiments, the term “curing” is understoodto refer to the process, for example, crosslinking by whichmacromonomers are converted into a three dimensional higher molecularweight polymer that is a solid, semi-solid, gel or combinations thereof.In certain embodiments, the term “curing” is understood to refer to thecrosslinking of the molecules in the injected composition to form asubstantially continuous network that may be a solid, semi-solid, gellike or combinations thereof. In certain embodiments, the term“substantially cured” is understood to refer to the formation of asubstantially continuous polymer network that may be a solid,semi-solid, gel-like or a combination thereof.

As used herein, the term “in situ” is understood to refer to thephenomenon, processes and/or results occurring in place.

As used herein, the term “capsule” is understood to refer to thecapsular bag of the eye of a warm blooded animal or an artificialsituation simulating the capsular bag of the eye such as capsular mouldsin a laboratory situation.

As used herein, the term “aqueous medium” is understood to refer towater based solutions, water, moisture or combinations thereof.

As used herein, the term “injectable” is understood to refer to theprocess or procedure by which the composition can be delivered orintroduced or transported or pumped by force through a tube or duct orpassage or canal or cavity or channel to the site of delivery i.e. thecapsule.

As used herein, the term “injectable composition” is understood to referto a composition that is capable of being injected. Typically, theinjectable composition refers to a composition that is not cured orsubstantially not cured. In certain applications, the injectablecomposition may be partially cured prior to being injected and/or placedin situ.

As used herein, the term “cannula” is understood to refer to devicesthat can be used to inject or deliver or introduce the composition tothe required site i.e. the capsule and includes cannula, cannula likedevices, needles, needle-like devices, tubes, tubing, catheters and alldevices with a bore used for injection or delivery of the composition tothe site.

As used herein, the term “syringe” is understood to refer to a device orinstrument that is used to hold and transport the composition to thesite and includes syringe, syringe like devices, cylinders, cartridges,pumps and all devices used for injection of the composition to the site.

As used herein, the term “extractables” is understood to refer to thecomposition and/or quantity of material removed into solution from acured macromonomer through the direct immersion of the cured polymer ina solvent that solubilizes suitable macromonomers, or higher oligomersthereof.

As used herein, the term “modulus” is understood to refer to thecompressive or shear force, measured in kPa, required to deform a curedmacromonomer.

As used herein, the term “mole fraction of the end groups” is understoodto refer to the ratio, or percentage, of polymer end groups that possessa hydrolysable and cross linkable moiety as compared with the totalnumber of polymer end groups available for functionalization. The “molefraction of functionalized end groups” may be determined by methodsusing Nuclear Magnetic Resonance (NMR) assessment and/or Gel PermeationChromatography (GPC) assessment in order to determine the molecularweight of the product. This may be followed by using either quantitativeNMR to determine the percentage of polymer end groups functionalizedand/or the titration of the polymer using a wet chemistry method toquantify the hydrolysis products generated in order to calculate thestoichiometry of the hydrolysis product to the number of available endgroups on the polymer (based on its molecular weight as determined byNMR and/or GPC).

The moisture curing capability is introduced to the macromonomer i.e.the organosilicon compound though the introduction of either or amixture of, silyl esters group as outlined in Structure A, and silylether groups as described in Structure B.

-   Where; R=R′=CH₃, CH₃CH₂—, CH₃CH₂CH₂—, (CH₃)₂CH—, and higher branched    and straight aliphatic chains, aromatic and substituted aromatic,    both of which may also contain heteroatoms such as N, S and    halogens.    -   R″=CH₃ or Ph or CH₃CH₂—, CH₃CH₂CH₂—, (CH₃)₂CH—, and higher        branched and straight aliphatic chains, aromatic and substituted        aromatic, both of which may also contain heteroatoms such as N,        S and halogens    -   R=CH₃ or Ph or CH₃CH₂—, CH₃CH₂CH₂—, (CH₃)₂CH—, and higher        branched and straight aliphatic chains, aromatic and substituted        aromatic, both of which may also contain heteroatoms such as N,        S and halogens    -   n=1, 2 or 3    -   G=Group attaching functionality to polymer, usually -(—O—)-, or        -(—CH₂CH₂—)-, resulting from the functionality being introduced        to the polymer through condensation, hydrosilation, or        nucleophilic substitution reactions.    -   m>1, and represents the polysiloxane component of the linear or        branched copolymer that constitutes the macromonomer        (organosilicon compound).

Both of these classes of siloxane are hydrolytically sensitive—reactingwith water, moisture and/or an aqueous medium to release the ester oralcohol hydrolysis product, and in the process, generating a silanolfunctionality. The silanol group may undergo further condensationreactions with other silanols, as well as with the precursor silyl esterand silyl ether groups. The silanol condensation reactions between thepolymer macromonomers may result in the crosslinking of themacromonomers into a continuous covalent network. For the purpose ofensuring a high degree of incorporation of the macromonomer into thecured composition siloxane functionalities bearing multiplefunctionality at the end of the polymer chains may be included. Scheme 1provides an example of a triethoxy-end group employed for a linearsiloxane resulting in hexafunctionality with respect to opportunitiesfor incorporation into matrix. Similarly Scheme 2 provides the exampleof the incorporation of a diacetoxymethyl end group on a linear siloxaneresulting in a tetrafunctional precursor macromonomer.

The benefits may be magnified with the use of a branched macromonomer asin Scheme 3.

Further, considerations may be given to the refractive index of thecomposition and as in Structures C and D. This may be achieved throughcopolymerization of cyclodimethylsiloxanes with phenyl siloxanes, ortheir equivalent hydrolozates to produce a polyphenyl-methyl-siloxane orpolydiphenylsiloxane copolymer as depicted in structures C and D.

Also, the desired molecular weight of the injectable composition may beachieved through the moderation of the end group (such as those depictedin Structures E(i) to (iii)) concentration during cationic ring openingpolymerisation (ROP), using such catalysts as triflic acid, sulphuricacid, or Amberlyst (Dow), or may be controlled in an anionicallyinitiated ROP through the ratio of monomer to “endcapper” (such as thosedepicted in Structure E(i) to (iii) or an initiatior (such as StructureF(i) and (ii)).

Also, branching within the composition may be introduced by a number ofways. For example, a symmetrical difunctional linear precursor may beused in a hydrosilation reaction with a polyfunctional core (Scheme 4aand 4b) with either vinyl end groups or hydride end groups on thepolymer chains.

Macromonomers (organosilicon compounds) with a range of desiredarchitectures may be generated by altering: the molecular weight of theprecursor polymer and/or the ratio of end-group functionalised polymerto core and/or the numerical functionality of the core(Tris(dimethyvinylsiloxy) phenylsilane (TDVPS)—3 arm core,(Tetrakis-(dimethylvinylsiloxy)-silane) (TDVS)—4 arm,1,3,5,7,9,11-Hexavinyl-5,9-dibutoxytricyclo[5.5.1.1(3,11)]hexasiloxane—6arm, etc). The residual functionalities remaining on the macromolecularoligomeric structure, which may be capable of undergoing hydrosilationchemistry (i.e. a Si—H or Si-Vinyl), are subsequently reacted in thepresence of a catalyst to introduce the hydrolisable and condensablesiloxane moiety. To deliver the functionality of the desired startingpolymer, hydrosilation reaction using dimethylethoxyvinylsilane,methyldiethoxyvinylsilane, triethoxyvinylsilane,diethoxymethylvinylsilane, vinyldiacetoxymethylsilane,vinyldimethylacetoxysilane may be used. Correspondingly for vinylterminated polymer chains; diethoxymethylsilane, diacetoxymethylsilane,dimethylethoxysilane, dimethylacetoxysilane, triethoxysilane may beused. Catalysts such as chloroplatinic acid, Karstedt's catalyst,palladium acetate and platinum oxide may be employed.

Initiators as the type described in figure F (ii) may have the advantageof producing narrow polydispersity functionalised macromers—relative tothe oligomeric type structures obtained by one pot hydrosilations asdisclosed in Scheme 4. Examples of the use of such initiators areincluded in Scheme 5 in order to demonstrate the applicability of sucharchitectures.

The following examples illustrate the process of preparation offunctionalization of the linear and/or branched macromonomer(organosilicon compound). It should be understood that what isillustrated is set forth only for the purposes of example and should notbe taken as a limitation on the scope of the present disclosure.

Example 1: Synthesis of Si—H Terminated 3.1:1 Branched PDMS Macromonomer

A stock solution of Tris (dimethyvinylsiloxy) phenylsilane stocksolution (TDVPS) was prepared by dissolving TDVPS (1.603 g) in 95.625 gof dry toluene (1.649%). Also diluted Karstedt's catalyst (Platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane catalyst) was prepared bydissolving 1 mL of Karstedt's catalyst (2% Pt in xylene) in dry toluene(100 mL).

Thereafter, DMS-H31 (Gelest) (30.928 g, 1.2315×10-3 mol), anhydroustoluene (80 mL), TDVPS stock solution (9.848 g, 3.973×10−4 mol) to give3.1:1 branched PDMS macromonomer and Karstedt's catalyst solution (1mL), were introduced to a three neck flask containing a magneticstirrer, connected to a condenser under nitrogen and the mixture wasstirred and heated for 2 h at 70° C. The completion of the reaction wasmonitored by 1H NMR. The disappearance of vinyl signals at around 6 ppmconfirmed the completion of the reaction, and the reaction flask wasremoved from the condenser. Anhydrous toluene (30 mL) was added todilute the mixture, followed by activated carbon, and the mixturestirred overnight at room temperature. A small amount of the reactionmix was withdrawn for characterisation. 1HNMR (CDCl3, ppm) δ=0.074(Si—(CH₃)₂, b), 0.18 ((CH₃)₂—Si—H, d), 0.45 (—CH₂—CH₂—, m), 4.706((CH₃)₂—Si—H, h), 7.25-7.7 (Aromatic H, m), GPC (THF): Mn: 46252, Mw:94463, Mw/Mn: 2.04, viscosity 13.34 Pa·s.

Example 2: Synthesis of Si—H Terminated PDMS Macromonomer: 3.2:1

The procedure was as outlined previously for 3.1:1 DMS-H31/TDVPS MMexcept that 47.66 g, 1.8978×10-3 mol DMS-H31 and TDVPS (1.603 g) wereused. 1H NMR (CDCl3, ppm) δ=0.068 (Si—CH3, b), 0.184 (CH3-Si—H, d),0.418 (—CH2-CH2-, b), 4.70 (CH3-Si—H, h), 7.25-7.7 (Aromatic H, m), GPC(THF): Mn: 45127, Mw: 91101, Mw/Mn: 2.02, viscosity 9.798 Pa·s

Examples 1 and 2 were repeated with a range of DMS-H31/TDMS ratios, withDMS-H25 (Gelest) and with various catalysts, to synthesise macromonomersas outlined in Tables 1 and 2.

TABLE 1 Synthesis of macromonomers in varying ratios n(Si—H GPC: THF* &polysyrene PDMS n(trisvinyl standards Viscosity Polymer H31) core) RatioCatalyst Mn Mw Mw/Mn (Pa · s) Starting material H31 25113 37732 1.501.30 1 3.1 1 3.1:1 Karstedt 46252 94463 2.04 13.34 2 3.2 1 3.2:1Karstedt 47107 91243 1.94 9.80 3 3.3 1 3.3:1 Karstedt 44178 87689 1.989.11 4 3.4 1 3.4:1 Karstedt 43441 86567 1.99 8.81 5 3.5 1 3.5:1 Karstedt42653 84238 1.97 7.92 6 3.6 1 3.6:1 Karstedt 42000 83694 1.99 7.45*THF—Tetrahydrofuran

TABLE 2 Synthesis of macromonomers in varying ratios Si—H n(Si—H GPC:THF* & polysyrene terminated PDMS n(trisvinyl standards Viscositymacromonomer H31) core) Ratio Catalyst Mn Mw Mw/Mn (Pa · s) Startingmaterial H31 26160 40359 1.5 1.30 1 3.0 1 3:1 PtO2 47566 127972 2.6916.77 2 4.0 1 4:1 PtO2 38568 92920 2.41 7.02 Starting materialprecipitated H31 26079 39281 1.51 1.75 3 3.0 1 3:1 PtO2 52291 1134092.17 30.00 Starting material H25 17200 4 3.0 1 3:1 PtO2 20511 46209 2.251.77 5 4.0 1 4:1 PtO2 20122 45621 2.27 1.53 Starting materialprecipitated H25 29255 42451 1.45 0.75 6 3.0 1 3:1 PtO2 22736 51610 2.271.89 *THF—Tetrahydrofuran

Example 3: Synthesis of α,ω-divinyl Terminated Mid-IndexMethylphenylsiloxy-PDMS Copolymer (Vt-PDMS-Co-PPMS) Via CationicPolymerisation

Octamethylcyclotetrasiloxane (40.5 g),1,3,5,7-phenylmethyl-cyclotetrasiloxane (mixture of D3Ph, D4Ph) (35.0g), divinyltetramethyldisiloxane (1.2 mL) and trifluoromethanesulfonicacid (40 uL) were stirred at room temperature for 24 hours. The reactionwas diluted with pentane (50 mL) and sodium carbonate (3 g) was addedand stirred for a further 24 hours. Thereafter, sodium carbonate saltwas filtered and solvent removed under vacuum. The resultant polymer waspurified by washing with 9% toluene in methanol, followed by 9% pentanein methanol. The majority of solvent was removed under low vacuum andresidue solvent removed under high vacuum. 1Hnmr (CDCl3, ppm)=−0.3-0.15ppm (Si—(CH₃)2, b), 0.16 ppm —CH2=CH2-Si—(CH₃)2, s), 0.2-0.42 ppm(−CH3-Si—Ph, b), 5.5-6.5 ppm (—CH2=CH2-, m), 7.2-7.6 ppm (Aromaticprotons, two b). % mole vinyl content: 1.76. GPC (toluene): Mn: 47496,Mw: 13547, Mw/Mn: 1.8.

Example 4: Synthesis of α,ω-divinyl Terminated Mid-IndexMethylphenylsiloxy-PDMS Copolymer (V-PDMS-Co-PMPS-V) by AnionicPolymerisation

D4 (150.50 g) and D3,4Ph (48.98 g) and a magnetic stirrer wereintroduced into a 500 mL 3 neck flask. The flask was connected to acondenser and the top of the condenser connected to a N2 line. The flaskwas sealed with a stopper and a septum. The reaction flask was flushedwith N2 for 30 mins. Then 40 mL of dry THF was added to dissolve themonomers and the flask was immerged into a 70 degrees oil bath for 20-30mins.

Potassium dimethylvinylsilane was weighed in 100 mL RBF in the dry boxand the flask sealed with a septum. 40 mL of dry THF was added todissolve silanolate which was then added to the monomer solution usingsyringes and then another 40 mL of dry THF was added to rinse thesilanolate flask to ensure that silanolate initiator was transferred tothe reaction flask. After the silanolate solution and the washing wereadded, the starting time for the reaction was recorded and left stirringat 70 degrees for 90 mins and then the reaction removed from the oilbath. A pale yellow and viscous mixture was observed. Thenchlorodimethylvinylsilane (1.4 mL) was added using a syringe. With theaddition of chlorosilane, the yellow colour disappeared and the reactionturned slightly hazy due to the formation of potassium chloride salt.The reaction was left to stir at room temperature for 3 h.

Thereafter, THF and excess chlorosilane were pumped out resulting in ahazy and viscous polymer was obtained. Methanol 8×250 mL was added andstirred for few mins. Then the reaction mix was let to stand for sometime to ensure that the polymer settled to the bottom of the flask andmethanol removed by decantation. Residue methanol was removed usingvacuum pump resulting in a transparent and viscous material.

¹H NMR (CDCl3, ppm) δ=0.074 (Si—(CH3)3, b), 0.158 (—(CH3)2-Si—CH═CH2),s), 0.288 (CH3-Si—Ph), 5.69-6.14 (—CH═CH2), 7-7.5 (Aromatic H, b),RI=1.431 and density=1.08467 g/mL. GPC(Toluene): Mn: 15,218, Mw: 33,392,Mw/Mn: 2.19

Example 5: Synthesis of α,ω-divinyl Terminated Mid-IndexMethylphenylsiloxy-PDMS Copolymer (Vt-PDMS-Co-PMPS) by EquilibriumAnionic ROP

Octamethylcyclotetrasiloxane, (113.6 g),1,3,5,7-phenylmethyl-cyclotetrasiloxane (mixture of D3, D4Ph,Me) (37.1g) and divinyltetramethyldisiloxane (2 g or 2.472 mL) were introducedinto a 500 mL three neck-flask. Dry THF (100 mL) and KOH pellets (2.3 g)were added and reaction heated at 70° C. under N2 for 24 h. Aftercooling, the reaction was diluted with hexane (100 mL) and transferredto a separating funnel. Milli-Q water (100 mL) was added and the mixturewas shaken. Two layers formed. The mixture in the separating funnel wasneutralised with a few mL of HCl (5M). The organic layer was dried withmagnesium sulphate (6 g). The magnesium salt was then filtered and thesolvent removed under high vacuum. The product was washed with methanoland residue methanol removed using a rotary evaporator followed byresidual solvent removed under high vacuum. 1HNMR (CDCl3, ppm)=−0.3-0.15 ppm (Si—(CH3)2, b), 0.16 ppm —CH2=CH2-Si—(CH3)2, s), 0.2-0.42ppm (—CH3-Si—Ph, b), 5.5-6.5 ppm (—CH2=CH2-, m), 7.2-7.6 ppm (Aromaticprotons, two b). % mole vinyl content: 1.07. GPC (toluene): Mn: 9,940,Mw: 20,203, Mw/Mn: 2.03. RI: 1.438; Viscosity: 2.752 Pa·s

Example 6. Synthesis of Trimethoxy Terminated 3.6:1 TDVPS/DMS-H31Branched Macromonomer

Dilution of Karstedt's catalyst (Platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane catalyst): Karstedt'scatalyst 2% Pt in xylene (1 mL) was dissolved in dry toluene (100 mL).

Si—H terminated macromonomer (25.77 g) made as in Example 1, wasintroduced to a flask with a magnetic stirrer, and connected to acondenser under nitrogen. Anhydrous toluene (130 mL), 0.371 mL oftrimethoxy vinyl silane and 1 mL of 0.02% Karstedt's catalyst solutionwere introduced into the reaction flask and the reaction mix stirredovernight at 70° C. under nitrogen atmosphere. The completion of thereaction was monitored by ¹H NMR. The disappearance of Si—H peaks at 4.7ppm confirmed the completion of the reaction. Then anhydrous toluene (20mL) was added to dilute the reaction mixture, followed by activatedcarbon and the mixture stirred overnight at room temperature.Thereafter, the carbon was filtered and toluene removed by rotaryevaporator. The residual solvent was removed using a high vacuum pump toyield the desired functionalised macromonomer. ¹H NMR (CDCl3, ppm)δ=0.0727 (Si—CH3, b), 0.4337 (—CH2-CH2-, b from Si—H staringmacromonomer), 0.572 (—CH2-CH2-, b), 3.574 (—OCH3, s), 7.26-7.31(Aromatic H, b).

Example 7. Synthesis of Acetoxy Terminated Branched Macromonomer

28.0 g of Si—H terminated macromonomer made as in Example 1 wasintroduced to a flask with a magnetic stirrer and connected to acondenser under nitrogen. Anhydrous toluene (40 mL), glacial acetic acid(0.16 mL) and a spatula tip of palladium acetate were introduced intothe reaction flask and the reaction mixture stirred overnight at 70° C.under nitrogen. The completion of the reaction was monitored by NMR. Thedisappearance Si—H peaks at 4.7 ppm confirmed the completion of thereaction. Anhydrous toluene (20 mL) was added to dilute the reactionmixture followed by activated carbon and the mix stirred overnight atroom temperature. The carbon was then filtered and the toluene removedby rotary evaporator. The residual solvent was removed using high vacuumpump. ¹H NMR (CDCl3, ppm) δ=0.068 (Si—CH3, b), 0.284 (CH3)2Si—O—CO—CH3s), 0.43 (—CH2-CH2-, b), 2.058 (—Si—O—CO—CH3, s), 7.26-7.31 (Aromatic H,b)

Example 8. Synthesis of Methoxy-Terminated Linear PDMS Via Hydrosilation

5 g of DMS-H31 (Gelest) (1.99×10-4 mol) and 2 g (1.35×10-2 mol) of vinyltrimethoxy silane (excess) were placed in a 100 mL round bottom flaskwith a magnetic stirrer. Toluene (20 mL) was added to dissolve thereactants followed by platinum oxide (PtO2) catalyst (50 mg) and themixture stirred at 70° C. for 2 hours. The reaction was monitored by ¹HNMR. The disappearance of the Si—H bond at δ=4.70 ppm confirmed thecompletion of the hydrosilation reaction. After purification by vacuumdistillation (Kugelrohr), the product was isolated as colourless liquid,which was characterized by 1H NMR spectroscopy. δppm, (0.067 Si—CH3, b),0.571 (—CH2-CH2-, b), (3.573-OCH3 s)

Example 9. Synthesis of Ethoxy-Terminated Linear PDMS Via Condensation

13 g (7.22×10⁻⁴ mol) of DMS-S27 (Gelest) was mixed with 20 mL (1.3×10⁻¹mol) of Methyl triethoxy silane (MeTEOS) and the reaction mixture wasconnected to a Dean Stark apparatus. The reaction mixture was heatedfrom ambient temperature to boiling over 15 min, and then refluxed for90 min. Excess MeTEOS was removed via Dean Stark apparatus. NMRconfirmed that the reaction had proceeded successfully, also indicatingthe presence of a small amount of residual MeTEOS—which was then removedby Kugelrohr apparatus. The product was isolated as colourless viscousoil that was characterized by ¹H NMR (0.067 Si—CH3, b), 3.515-OCH3 s).

Example 10. Synthesis of Ethoxy-Terminated Linear PDMS ViaHydrosilylation

5 g of DMS-H31 (1.99×10⁻⁴ mol) and 2 mL (9.49×10⁻³ mol (excess) ofDiethoxy (methyl)vinylsilane were placed in a 100 mL round bottom flaskwith a magnetic stirrer. Toluene (20 mL) was added to dissolve thereactants followed by platinum oxide (PtO2) catalyst (50 mg) and themixture stirred at 70° C. for 2 hours. The reaction progress wasfollowed by ¹H NMR. The disappearance of the Si—H bond at δ=4.70 ppmconfirmed the completion of the hydrosilation reaction. Reaction mixturewas filtered to remove the platinum catalyst. After purification bydistillation, removal of excess diacetoxymethylvinylsilane was achievedthrough heating under vacuum (Kugelrohr), and the product isolated as acolourless oil, which was characterized by ¹H NMR (0.067 Si—CH₃, b),0.571 (—CH₂—CH₂— b), 3.83 (—CH₂—) q), 1.23 (—CH₃, t).

Example 11. Synthesis of Ethoxy-Terminated Linear PDMS Via Condensation

6.26 g of DMS-S35 (Gelest) was mixed with 20 mL of Tetraethylorthosilicate (TEOS) and the reaction mixture connected to a Dean Starkapparatus. The reaction mixture was heated from ambient temperature toboiling over 15 min and refluxed for 90 min. Excess MeTEOS was removedvia Dean Stark apparatus. NMR confirmed that the reaction proceeded tocompletion, but indicated the presence of trace residues of MeTEOS,which were removed by heating on a Kugelrohr under high vacuum. Theproduct was isolated as colourless oil. (0.072 Si—CH₃, b), (1.245 CH₂—CH₃, t,) (3.863 CH ₂—CH₃, q).

Example 12. Synthesis of Acetoxy Terminated Linear PDMS Using PalladiumAcetate

DMS-H31 (30 g, 1.147×10-3 mol) was weighed in a 250 mL three neck flaskcontaining a magnetic stirrer. The reaction flask was connected to acondenser with a nitrogen gas inlet and purged with a positive pressureof nitrogen gas. Anhydrous toluene (50 mL), glacial acetic acid (0.05mL) and a small spatula tip of palladium acetate was introduced to thereaction and stirred overnight at 70° C. The colour of the reactionmixture turned dark brown as the reaction progressed. The progress ofthe reaction was monitored by ¹H NMR. The disappearance of Si—H peaks at4.7 ppm confirmed the completion of the reaction, and activated carbonwas added, and the reaction mixture stirred overnight at roomtemperature. Thereafter, the carbon was filtered and the toluene removedby rotary evaporator. The residue solvent was removed using high vacuumpump to obtain a transparent polymer. 1HNMR (CDCl3, ppm) δ=0.0701(Si—CH3, b), 0.287 (CH3)2Si—O—CO—CH3, s), 2.0589 (—Si—O—CO—CH3, s).

Example 13: Synthesis of Hydroxyl Terminated PDMS-Co-PMPS

Octamethylcyclotetrasiloxane, (37.754 g) and Phenylmethyl-cyclosiloxanes(mixture of D3Ph,Me, D4Ph,Me) (12.264) were placed into a flaskconnected to a condenser under nitrogen. Dry THF (50 mL), and KOH (60mg) were added. The reaction mixture was heated at 70° C. with stirringfor 24 h. Milli-Q water (0.5 mL) was added followed by the removal ofTHF under vacuum. The reaction mixture was diluted by adding hexane (100mL) and transferred to a separating funnel. Milli-Q water (100 mL) wasadded and the mixture shaken. Two layers formed. The reaction mixturewas neutralised by adding 0.1M HCl until the pH of the aqueous layer was7. The aqueous was discarded, and the organic layer washed with Milli-Qwater (4×100 mL), transferred to a conical flask, added magnesiumsulphate (3 g) and the mixture stirred at room temperature to dry theproduct. The product was washed with methanol (100 mL×3), with residuemethanol removed using vacuum. 1Hnmr (CDCl3, ppm)=−0.2-0.18 (Si—(CH3),b), 0.2-0.45 (CH3)-Si—Ph), (7.25-7.7 (Aromatic H, m). GPC: Mn: 18160,Mw: 47579, Mw/Mn: 2.62. Viscosity: 2.752 Pa·s. RI: 1.438 and density:1.096 g/mL.

Example 14. Diacetoxy Terminated Linear Polydimethyl-Co-PolyphenylmethylSiloxane Copolymer

Silanol terminated PDMS-co-PPMS was diluted in anhydrous tetrahydrofuranand added dropwise to a large excess of methyltriacetoxysilane that wasin a liquid state due to the addition of a small amount oftetrahydrofuran. The mixture was allowed to stir for two days at roomtemperature.

The product was mixed with anhydrous acetonitrile which precipitated thesiloxane (The excess methyltriacetoxy silane remained solubilised in theco-solvent layer). Upon separation the solvent was removed by vacuum.NMR (CDCl3, ppm)=0.0760 (Si—CH3, b), 0.318 (Ph—Si—CH3, b), 0.506((AcO)2-Si—CH3, s), 2.099 (CH3-Si—(OOCCH3)2, s), 7.25-7.7 (Aromatic H,m). Viscosity 5.63 Pa·s.

Example 15: Preparation of Diethoxy Functionalised 3.1:1 Branched PDMSMacromonomer

Si—H terminated macromer (25.77 g) made as in Example 1 was dissolved in160 mL of dry toluene, introduced to a flask with a magnetic stirrer andconnected to a condenser under nitrogen. Diethoxy methylvinylsilane(0.47 mL) and 1 mL of Karstetd's catalyst solution were introduced tothe reaction flask and the mix stirred overnight at 70° C. undernitrogen atmosphere. The completion of the reaction was monitored by 1HNMR. The disappearance Si—H peaks at 4.7 ppm confirmed the completion ofthe reaction. Then anhydrous toluene (20 mL) was added to dilute thereaction mixture followed by activated carbon and stirred overnight atroom temperature. Then the carbon was filtered and toluene was removedby rotary evaporator. The residue solvent was removed using high vacuumpump and a viscous polymer was obtained. ¹H NMR (CDCl3, ppm): 0.071(Si—CH₃, b), 0.439 (—CH₂—CH₂—, b from Si—H staring macromolecule), 0.522(—CH₂—CH₂—, b), 1.22 (Si—O—CH₂—CH₃, t), 3.78 (Si—O—CH₂—CH₃, q),7.26-7.31 (Aromatic H, m).

Example 16: Synthesis of Diacetoxy Functionalised LinearPolydimethylsiloxane-Co-Polydiphenylsiloxane

Vinyl terminated (15-17% Diphenylsiloxane)-Dimethylsiloxane copolymer,PDV-1631, Gelest (52.12 g, 2.74×10-3 mol) and diacetoxy methyl silane(1.77 g, 1.1×10-3 mol) were placed in a round bottom flask with amagnetic stirrer in a glove box. Toluene (250 mL) was added to dissolveboth compounds. 1 mL of Karstedt's catalyst, Pt(dvs), (2 mM solution inToluene) was added and reaction mixture stirred at 70° C. overnight. Theprogress of the reaction was monitored by ¹H NMR. The disappearance ofthe double bond from PDV-1631 confirmed that the reaction was completed.The bulk of solvent was removed via rotary evaporator, with theremaining toluene/excess of starting diacetoxy methyl silane removedunder high vacuum. The product was obtained as a transparent and viscousliquid.

¹H NMR: δ=0.08 (CH3)2; 0.51 CH2; 2.103 COCH3; 7.31-7.58 Ph)

Example 17: Synthesis of Diacetoxy Functionalised 3.6:1 BranchedPDMS-Co-PPMS Polymer

Methylphenyl-PDMS copolymer (46.09 g, 4.64×10−3 mol) andphenyltris(dimethylsiloxy)silane core (0.426 g, 1.288×10-3) (mol) wereplaced in a round bottom flask equipped with a magnetic stirrer in aglove box. Toluene (200 mL) was added to dissolve both compounds.Karstedt's catalyst, Pt(dvs), (1 mL of 2 mM solution in Toluene) wasadded and reaction mixture stirred at 70° C. for 4 hours. The progressof hydrosilylation was monitored by 1H NMR. The disappearance of Si—Hbond from phenyltris(dimethylsiloxy)silane core indicated that thehydrosilylation was completed. Diacetoxymethylsilane (1.49 mL, 9.27×10-3mol) was added and the reaction mix stirred overnight. Disappearance ofthe double bond shift confirmed the completion of the secondhydrosilylation. The reaction mixture was further stirred overnight withactivated carbon to remove Karstedt's catalyst, filtered and reduced byremoving bulk of solvent under N2 via rotary evaporator. The remainingtoluene/excess of starting diacetoxy methyl silane was removed underreduced pressure while the product was kept in the glove box. Theproduct was obtained as a transparentand viscous liquid. Properties ofbranched acetoxy mid index polymer are: Viscosity—4.37 Pa·s.

Example 18: Synthesis of Polymer Macromolecule with ReducedPolydispersity and Defined Architecture

1,3,5-Tris(dimethylsilanol)benzene (50 mg, 0.17 mmol) was dissolved inanhydrous THF (50 mL) in a dried RB flask under argon. 2.5 M BuLisolution in hexanes (0.20 mL, 0.50 mmol BuLi) was added and the solutionstirred for 5 min. Separately, D₃ (10 g, 45 mmol) was weighed into adried RB flask under argon and dissolved in anhydrous THF (30 mL). Thismonomer solution was added to the initiator solution and stirred at roomtemperature for 2 h. Chlorodimethylsilane (1 mL, 10 mmol) was added andthe mixture stirred for 2 h before being concentrated in vacuo (20 mbar,50° C.) to afford a milky oil. Anhydrous pentane (ca. 3× the volume ofpolymer) was added and the solution stirred under argon for 30 min. Theinsoluble lithium salts were filtered under argon and the filtrateconcentrated in vacuo (20 mbar, 40° C.), followed by drying in vacuo(0.1 mbar, 120° C., 14 h), to afford the hydride-terminated star polymeras a colourless viscous oil.

Example 19: Functionalisation of Reduced Polydispersity and DefinedArchitecture to Produce Diacetoxy Terminated Macromonomer

20.08 g of branched silanol terminated siloxane copolymer (Example 18.Silanol 100 kg/mol theoretical weight, PDI 1.3) was dissolved in 90 mLof anhydrous tetrahydrofuran and dried over magnesium sulphate. Thismixture was then passed over activated neutral aluminium oxide followedby its dropwise addition into a vigorously stirring mixture of 16.54 mLof dimethyl diacetoxy silane and 0.206 mL of methyl triacetoxy silane. Afurther 90 mL of anhydrous tetrahydrofuran was added once the siloxanecopolymer addition through the column was completed. Purificationoccurred by the addition of 300 mL of anhydrous acetonitrile whichprecipitated the product. A second precipitation was performed by theaddition of 10 mL of anhydrous tetrahydrofuran and then 50 mL ofanhydrous acetonitrile. Once separated the product was put under vacuumto remove trace levels of solvent.

¹HNMR (CDCl3, ppm)=−0.12-0.16 (Si(CH3)₂O, b) 0.16-0.37 (SiCH₃PhO, b),0.367 (—Si(CH3)(Ar core), s), 0.518 ((AcO)2-Si—CH3, s), 2.107(CH3-Si—(OOCCH3)₂, s), 7.25-7.7 (Aromatic H, b), 7.77 (3ArH core, s).Viscosity 1.252 Pa·s.

Example 20: Synthesis of α,ω-divinyl Terminated Mid-Index PDMS-Co-PMPSCopolymer by Anionic Ring Opening Polymerisation-KOH

D4 (113.6 g), D3,4 Ph mix cyclics (37.1 g), anddivinyltetramethyldisiloxane (2.47 mL), dry THF (100 mL), KOH (0.25 g)were charged into a 500 mL round bottom flask equipped with a magneticstirrer (dry box). The reaction flask was brought outside, connected toa Nitrogen gas and stirred at 70° C. for 20 hours. After the reactionmix temperature was brought ambient it was neutralised with Pentane (100mL), milli-Q water (100 mL) and 5M HCl (0.5 mL) and stirred at roomtemperature for 30 mins. The reaction mix was then transferred into aseparating funnel, mixed vigorously; bottom aqueous layer was discarded.Milli-Q water (100 mL) was added to the organic layer and the mix wasshaken vigorously; the bottom aqueous layer was removed. The organiclayer was washed with milli-Q water for three more times until the pH ofthe aqueous layer was around 5-6 (the pH of the mill-Q water). Theorganic layer was transferred into a conical flask and stirred withmagnesium sulphate (7.47 g) overnight at RT. The suspension wastransferred into an in house filtration unit and the salt was filteredoff. The solvent was removed by rotary evaporator and vacuum pumpovernight at room temperature to afford a clear polymer. The polymer waswashed with methanol (70 mL) for 8 times until GPC showed no presence ofthe low molecular weight oligomers. The solvent was removed using rotaryevaporator and vacuum pump at room temperature. A product was obtainedwas obtained that on a visual inspection was substantially colourlessand substantially transparent.

¹H NMR (CDCl₃, ppm) δ=−0.05-0.2 (Si—(CH₃)₂), b), 0.1703(CH₂═CH—Si—(CH₃)₂, s), 0.22-0.38 (—CH₃—Si—Ph, b), 5.6-6.2 (CH₂═CH—, m),7.2-7.6 (Aromatic protons, two b). Mn: 10,232, Mw: 18,658, Mw/Mn: 1.8.RI: 1.438.

Example 21: Synthesis of Diacetoxy Functionalised Macromonomerfromα,ω-divinyl Terminated Mid-Index PDMS-Co-PMPS Copolymer

α,ω-divinyl terminated mid-index PDMS-co-PMPS copolymer (50 g) andanhydrous toluene (250 mL) were introduced into a 500 mL one neck flaskcontained a magnetic stirrer and the reaction mix was mixed well.Phenyltris(dimethylsiloxy) silane (449 μL) and Karstedt's catalystsolution (1 mL) were added to the reaction mix. The reaction flask wasstirred for 4 h at 70° C. The completion of the first reaction wasmonitored by ¹H NMR; the disappearance of Si—H signals at around 4.7 ppmconfirmed that the reaction was completed. Then diacetoxymethylsilane(1.3 mL) and Karstedt's catalyst (0.5 mL) were added to the reactionmix, stirred at 70° C. overnight. The reaction was monitored by NMR. Thedisappearance of the Si—H bond confirmed hydrosilylation. The reactionwas stopped and activated carbon (4 g) was added and the reaction mixand stirred overnight at room temperature. The carbon was filtered offand toluene was removed by rotary evaporator and high vacuum pump (drybox). A product was obtained was obtained that on a visual inspectionwas substantially colourless and substantially transparent.

¹H NMR (CDCl₃, ppm) δ=−0.05-0.2 (Si—(CH₃)₂, b), 0.2-0.38 (—CH₃—Si—Ph,b), 0.43 (—CH₂—CH₂—, m, obtained from 1^(st) hydrosilylation reaction),0.51 and 0.939 ((—CH₂—CH₂—, m, obtained from 2^(nd) hydrosilylationreaction), 0.502 ((CH₃—Si—(O—CO—CH₃)₂, s), (2.11 (—Si—(O—CO—CH₃)₂, s),5.6-6.2 (CH₂═CH—, m, very low in intensity), (7.25-7.7 (Aromatic H, m),Mn: 14458; Mw: 55,135; Mw/Mn: 3.2; RI: 1.439; specific gravity: >1;viscosity: 3.93 Pa·s.

Example 22 below illustrates the process of preparation of the linearand/or branched macromonomer (organosilicon compound) that is partiallyfunctionalised, according to certain embodiments.

Example 22: Synthesis of Diacetoxy Functionalised Macromonomer fromα,ω-divinyl Terminated Mid-Index PDMS-Co-PMPS Copolymer (70% Diacetoxy,Core to Arm 3.85:1)

α,ω-divinyl terminated mid-index PDMS-co-PMPS copolymer (Mn10,937, 42 g)and anhydrous toluene (250 mL) were introduced into a 1 L 3 neck flaskthat contained a magnetic stirrer and the reaction mix was mixed well at70° C. Phenyltris (dimethylsiloxy) silane (350 μL) and Karstedt'scatalyst solution (0.78 mL) were added to the reaction mix. The reactionflask was stirred for 5 h at 70° C. Then diacetoxymethylsilane (0.5 mL)and Karstedt's catalyst (0.4 mL) were added to the reaction mix, stirredat 70° C. overnight. The reaction was cooled down to ambient andactivated carbon (7 g) was added. The reaction mix stirred overnight atroom temperature. The carbon was filtered off and toluene was removed byrotary evaporator and high vacuum pump (dry box). A product was obtainedwas obtained that on a visual inspection was substantially colourlessand substantially transparent. Mn: 19,967; Mw/Mn: 6.1: RI: 1.4403;Specific gravity: 1.02. [

Example 23: Synthesis of Diacetoxy Functionalised Macromonomer fromα,ω-divinyl Terminated Mid-Index PDMS-Co-PMPS Copolymer (85% Diacetoxy,Core to Arm 3.85:1)

α,ω-divinyl terminated mid-index PDMS-co-PMPS copolymer (Mn10648, 42.65g) and anhydrous toluene (250 mL) were introduced into a 1 L 3 neckflask contained a magnetic stirrer and the reaction mix was mixed wellat 70° C. Phenyltris (dimethylsiloxy) silane (365 μL) and Karstedt'scatalyst solution (0.78 mL) were added to the reaction mix. The reactionflask was stirred for 5 h at 70° C. Then diacetoxymethylsilane (0.62 mL)and Karstedt's catalyst (0.40 mL) were added to the reaction mix,stirred at 70° C. overnight. The reaction was cooled down to ambient andactivated carbon (7 g) was added. The reaction mix stirred overnight atroom temperature. The carbon was filtered off and toluene was removed byrotary evaporator and high vacuum pump. A product was obtained wasobtained that on a visual inspection was substantially colourless andsubstantially transparent. Mn: 21210; Mw: 116,613; Mw/Mn: 5.5; RI:1.4423; Specific gravity: 1.02.

End-group variations: Using the approach outlined above various starpolymers were prepared with different end-groups introduced by selectionof the reactive species during the quenching step; e.g., acid chlorideswere used to introduce mono-silyl ester end-groups; chlorosilanes wereused to introduce hydride, vinyl and triethoxy end-groups, and ammoniumchloride was used to introduce silanol groups. Characterisation of thesepolymers is provided below.

Silyl benzoate terminated star polymers with poly[(dimethylsiloxane)-ran-(methylphenyl siloxane)]-based were prepared via quenchingwith benzoyl chloride (270 equiv. relative to the initiator); ¹H NMR(300 MHz, CDCl₃) δ_(H)−0.124-0.362 (m, Si(CH₃)₂ and SiCH₃Ph polymerbackbone), 7.07-7.61 (m, ArH polymer backbone) 7.66-7.72 (m, ArHend-groups), 8.13-8.19 (in, ArH end-groups) ppm. GPC (relative toconventional linear polystyrene column calibration) M_(w)=72,000 Da;PDI=2.4.

Silyl hexanoate terminated star polymers with poly(dimethylsiloxane)-based arms were prepared via quenching with hexanoyl chloride(120 equiv. relative to the initiator); ¹H NMR (300 MHz, CDCl₃) δ_(H)0.076 (br s, Si(CH₃)₂ polymer backbone), 0.86-0.92 (m, CH₂CH₃end-groups), 1.27-1.32 (m, CH₂CH₂CH₃ end-groups), 1.58-163 (m, CH₂CH₂CH₂end-groups), 2.26-2.31 (m, O(CO)CH₂CH₂ end-groups), 7.78 (s, ArH core)ppm. GPC (relative to conventional linear polystyrene columncalibration) M_(w)=100,000 Da; PDI=2.0.

Silyl acetate (i.e., acetoxy) terminated star polymers withpoly(dimethyl siloxane)-based arms were prepared via quenching withacetyl chloride (120 equiv. relative to the initiator); ¹H NMR (300 MHz,CDCl₃) δ_(H) 0.076 (br s, Si(CH₃)₂ polymer backbone), 2.05 (br s,O(CO)CH₃ end-groups), 7.77 (s, ArH core) ppm. GPC (relative toconventional linear polystyrene column calibration) M_(w)4=88,000 Da;PDI=1.3.

Vinyl terminated star polymers with poly[(dimethylsiloxane)-ran-(methylphenyl siloxane)]-based anus were prepared viaquenching with chloro(dimethyl)vinylsilane (30 equiv. relative to theinitiator); ¹H NMR (300 MHz, CDCl₃) δ_(H)−0.082-0.359 (m, Si(CH₃)₂ andSiCH₃Ph polymer backbone), 5.73 (dd, J=4.2 & 20 Hz, ═CHH end-groups),5.93 (dd, J=4.2 & 15 Hz, ═CHH end-groups), 6.13 (dd, J=15 & 20 Hz,SiCHCH₂ end-groups), 7.09-7.61 (m, ArH polymer backbone) ppm. GPC(relative to conventional linear polystyrene column calibration)M_(w)=58,000 Da; PDI=1.5.

Hydride terminated star polymers with poly(dimethyl siloxane)-based armswere prepared via quenching with chlorodimethylsilane (60 equiv.relative to the initiator); ¹H NMR (300 MHz, CDCl₃) δ_(H) 0.077 (br s,Si(CH₃)₂ polymer backbone), 0.19 (d, J=3 Hz, SiH(CH₃)₂ end-groups), 0.35(s, ArSi(CH₃)₂ core), 4.71 (hept, J=3 Hz, SiH(CH₃)₂ end-groups), 7.77(s, ArH core) ppm; M_(n(NMR))=43,000 Da. GPC (relative to conventionallinear polystyrene column calibration) M_(w)=31,000 Da; PDI=1.2.

Triethoxy siloxane terminated star polymers with poly(dimethylsiloxane)-based arms were prepared via quenching withchlorotriethoxysilane (60 equiv. relative to the initiator); ¹H NMR (300MHz, CDCl₃) δ_(H) 0.076 (br s, Si(CH₃)₂ polymer backbone), 1.21 (t,J=6.9 Hz, OCH₂CH₃ end-groups), 3.78-3.87 (m, OCH₂CH₃ end-groups), 7.78(s, ArH core) ppm. GPC (relative to conventional linear polystyrenecolumn calibration) M_(w)=46,000 Da; PDI=1.4.

Silanol terminated star polymers with poly[(dimethylsiloxane)-ran-(methylphenyl siloxane)]-based arms were prepared viaquenching with ammonium chloride (60 equiv. relative to the initiator);¹H NMR (300 MHz, CDCl₃) δ_(H) −0.111-0.362 (m, Si(CH₃)₂ and SiCH₃Phpolymer backbone), 7.09-7.62 (m, ArH polymer backbone), 7.78 (s, ArHcore) ppm. GPC (relative to conventional linear polystyrene columncalibration) M_(w)33,600 Da; PDI=1.4.

Blending

In addition to above examples, blends with modifications in materialproperties may be prepared by mixing various percent concentrations(v/v) of diacetoxy terminated polydimethyl siloxane (DMS-D33) andbranched macromonomer material (Diacetoxy terminated polydimethylsiloxane (Gelest)).

The composition of the above examples is loaded into a suitableinjection device for injection into the capsular bag of the eye of awarm blooded animal or similar conditions such as for example, acapsular mould. The injection device may further comprise a syringe anda cannula. Once injected, the duration within which the composition maybe substantially cured may range from minutes to days.

Determination of Extractables

The substantially cured polymer is removed from the capsular mould, blotdried and the initial weight recorded. Thereafter, the substantiallycured polymer is soaked in pentane or suitable solvent for 3 days atroom temperature. The extracted solvents are combined, centrifuged,filtered and dried to constant weight.

The percentage of extractable is calculated by dividing the extractablecollected to the initial weight.

% Extractable=extractable collected/initial weight×100

Measurement of Modulus

For the determination of shear modulus, cured samples (at various curetimes and temperatures) were investigated by TA instruments AR1000rheometer. Experiments were conducted in oscillatory time sweep modeusing a 20 mm steel plate. Samples applied to the peltier plate wereexposed to a normal force of 0.2N. Upon reaching an equilibriumtemperature of 37° C., operating parameters involved a frequency of 1.0Hz and oscillatory stress of 125.0 Pa. This was employed to determine G′in units of kPa.

For the determination of compressive modulus, a custom built“microtensometer” that can measure mechanical properties of small andsoft material samples, including compression and tensile modulus,toughness, creep and stress relaxation is used. Its two major componentsare a precision motorised linear actuator and a precision analyticalbalance, both controlled by dedicated application software. For thecompression modulus testing of either explanted natural or refilledcrystalline lenses or gel materials in disc or lens shape, the sample isloaded into the instrument using corresponding sample holders thatprovide full support at the underside of the sample. The sample iscompressed from the top by the flat end face of a 2 mm diameter metalpin, which is attached to the linear actuator to be moved in a verticaldirection. After loading the sample into the instrument, the pin movesdownwards until it touches the sample surface. From the motor position,the actual sample thickness is calculated. The sample is then slowlycompressed by 10% of its original thickness, while motor position andbalance readings are acquired continuously. After reaching the presetcompression, the motor moves back to the start position and after somerecovery time, the measurement is repeated twice. Both readings areconverted to obtain the stress/strain curves. Linear lines are fittedthrough the data points between 4% and 8% range. The averaged slope ofthese lines is the compression Young's modulus.

Shear Modulus Testing of Oven Cured Macromonomers

Samples were ejected into a 20 mm diameter polyoxymethylene mould tocreate a 600 mg sample measuring 2 mm in thickness. Moulds were cured at35° C. for 24 hrs in a humid environment. This provided samples suitablefor rheological modulus testing.

A sample of diacetoxy functionalised 3.6:1 branched PDMS-co-PPMS polymerfrom Example 17 was oven cured for 24 hours and the shear modulusmeasured on the AR1000 determined to be 0.599 kPa.

A sample of diacetoxy functionalised linear PDMS-co-PDPS polymer fromExample 16 was oven cured and the shear modulus measured on the AR1000determined to be 0.64 kPa.

Compressive Modulus Testing of In Vitro Membrane Cured Macromonomers

A 0.3 mL sample of diacetoxy functionalised 3.6:1 branched PDMS-co-PPMSpolymer macromonomer from Example 17 was tied in medical grade collagenand immersed in 0.3 mL of Barany's solution at 37° C. for 7 days. Themodulus of the cured material was measured on the microtensometer at 5.6kPa.

A 0.3 mL sample of the diacetoxy functionalised reduced polydispersityof Example 19 was tied in medical grade collagen and immersed in 0.3 mLof Barany's solution at 37° C. for 7 days. The modulus of the curedmaterial was measured by rheology. The shear modulus was 1.3 kPa; andthe compressive modulus was 3.9 kPa.

A 0.3 mL sample of the diacetoxy functionalised macromonomer of Example21 was tied in medical grade collagen and immersed in 0.3 mL of Barany'ssolution at 37° C. for 7 days. The modulus of the cured material wasmeasured by rheology. The shear modulus was 1.7 kPa.

A 0.3 mL sample of the diacetoxy functionalised macromonomer of Example22 was tied in medical grade collagen and immersed in 0.3 mL of BSSsolution at 37° C. for 3 days. The modulus of the cured material wasmeasured by rheology. The compressive modulus was 2.5 kPa.

A 0.3 mL sample of the diacetoxy functionalised macromonomer of Example23 was tied in medical grade collagen and immersed in 0.3 mL of BSSsolution at 37° C. for 3 days. The modulus of the cured material wasmeasured by rheology. The compressive modulus was 5.5 kPa.

Shear Modulus Testing of Oven Cured Blends

A range of blend ratios, using various macromonomers reported in thepreceding examples, were prepared and assessed.

A blend of 70% trimethoxy terminated 3.6:1 TDVPS/DMS-H31 branchedmacromonomer of the type from Example 6, and 30% DMS-D33 (Gelest) wasoven cured for 24 hours and the shear modulus measured on the AR1000determined to be 2.23 kPa.

A blend of 70% trimethoxy terminated 3.1:1 TDVPS/DMS-H31 branchedmacromonomer, and 30% DMS-D33 (Gelest) was oven cured for 24 hours andthe shear modulus measured on the AR1000 determined to be 1.1604 kPa.Extractables 5.24%

A blend of 60% diethoxy terminated 3.1:1 TDVPS/DMS-H31 branchedmacromonomer, and 40% DMS-D33 (Gelest) was oven cured for 24 hours andthe shear modulus measured on the AR1000 determined to be 0.262 kPa.Extractables 3.7%.

A blend of 70% diethoxy terminated 3.1:1 TDVPS/DMS-H31 branchedmacromonomer, and 30% DMS-D33 (Gelest) was oven cured for 24 hours andthe shear modulus measured on the AR1000 determined to be 2.79 kPa.Extractables 5.11%.

Results of In Vivo Evaluation

A homogeneous blend (achieved by mixing 3 mL of DMS-D33 (Gelest) with 7mL of diethoxy functionalised 3.6:1 branched PDMS macromonomer (Table 1)(30/70 v/v) was prepared, and transferred to a syringe.

1 female adult anaesthetised NZW rabbits underwent surgery in one eyewherein an anterior peripheral continuous mini-capsulorhexis of thecrystalline lens capsule of approximately 1.0 mm diameter was performed,and the contents of the crystalline lens aspirated. After removal of theentire contents of the lens (nucleus and cortex), the capsular bag wasrefilled with a moderate quantity of viscoelastic to allow the insertionof a Mini-Capsular Valve (MCV; U.S. Pat. No. 6,358,279), to preventleakage of the macromonomer during lens refilling from the bag into theanterior chamber. After the appropriate insertion of the MCV through thecapsulorrhexis opening, the viscoelastic was emptied and the capsularbag refilled with the macromonomer blend. Using the slit-lampilluminator mounted on the operation microscope, complete refilling wasconfirmed. On post-operative day 11, the animal was sacrificed and theformed intraocular lens removed (explanted) and subjected to mechanicaltesting, the results of which are presented below.

Post Explanted lens - Modulus [kPa] Sample operative days Repeat 1Repeat 2 Repeat 3 11 3.4 3.2 3.3

Additional examples of exemplary non-limiting embodiments are providedin numbered paragraphs below. Any reference to a numbered paragraph isreference to a paragraph within this section.

Example A1

An injectable composition for forming an accommodating intraocular lensin situ in a capsule, comprising

-   -   an organosilicon compound and    -   a hydrolytically sensitive siloxane moiety    -   wherein the injectable composition has a specific gravity        greater than about 0.95, a number average molecular weight        (M_(n)) greater than about 5,000, a weight average molecular        weight (M_(w)) greater than about 20,000 and is capable of being        substantially cured in situ upon contact with moisture.

A2. The injectable composition of example A1, wherein the organosiliconcompound comprises linear polysiloxane polymer chains, linear polysiloxane copolymer chains, branched polysiloxane polymer chains, orcombinations thereof.

A3. The injectable composition of examples A1 or A2, wherein theinjectable composition has a specific gravity in the range of about 0.96to about 1.06.

A4. The injectable composition of example A1 or A2, wherein theinjectable composition has a specific gravity in the range of about 0.99to about 1.05.

A5. The injectable composition of example A1 or A2, wherein theinjectable composition has a specific gravity in the range of 1 to 1.04.

A6. The injectable composition of one or more of examples A1 to A5,wherein the hydrolytically sensitive siloxane moiety comprises one ormore of silane ether groups and/or one of more groups of silane estergroups.

A7. The injectable composition of one or more of examples A1 to A6,wherein the number average molecular weight (M_(n)) is in the range ofabout 5,000 to 150,000.

A8. The injectable composition of example A7, wherein the number averagemolecular weight (M_(n)) is in the range of about 5,000 to 100,000.

A9. The injectable composition of examples A7 or A8, wherein the whereinthe number average molecular weight (M_(n)) is in the range of about5,000 to 50,000.

A10. The injectable composition of one or more of examples A1 to A7,wherein the weight average molecular weight (M_(w)) is in the range ofabout 20,000 to 300,000.

A11. The injectable composition of example A10, wherein the weightaverage molecular weight (M_(w)) is in the range of about 20,000 to200,000.

A12. The injectable composition of example A10 or A11, wherein theweight average molecular weight (M_(w)) is in the range of about 20,000to 100,000.

A13. The injectable composition of one or more of examples A1 to A12,wherein the injectable composition has a viscosity greater than about0.5 Pa·s.

A14. The injectable composition of example A13, wherein the injectablecomposition has a viscosity between 0.5 to 30 Pa·s.

A15. The injectable composition of one or more of examples A1 to A14,wherein the injectable composition has mole fractions of the end groupsthat possess a hydrolysable moiety and cross linkable moiety in therange of greater than about 20%.

A16. The injectable composition of example A15, wherein the injectablecomposition has mole fractions of the end groups that possess ahydrolysable moiety and cross linkable moiety in the range of about 20%to 100%.

A17. The injectable composition of example A15 or A16, wherein theinjectable composition has mole fractions of the end groups that possessa hydrolysable moiety and cross linkable moiety in the range of about20% to 80%.

A18. The injectable composition of one or more of examples A1 to A17,wherein the hydrolytically sensitive siloxane moiety is capable uponcontact with moisture to generate one or more reactive silanol groupsand hydrolysis products.

A19. The injectable composition of example A18, wherein the injectablecomposition is substantially cured through condensation of one or morereactive silanol groups.

A20. The injectable composition of example A19, wherein the injectablecomposition is capable of being substantially cured and thesubstantially cured composition has a refractive index in the range ofabout 1.4 to about 1.5.

A21. The injectable composition of example A20, wherein the injectablecomposition is capable of being substantially cured and thesubstantially cured composition has a refractive index in the range ofabout 1.41 to about 1.45.

A22. The injectable composition of examples A20 or A21 wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has a refractive index in the range ofabout 1.42 to about 1.44.

A23. The injectable composition of one or more of examples A20 to A22,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has a refractive index ofat least 1.4.

A24. The injectable composition of one or more of examples A19 to A23,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has a modulus ofelasticity of about 6 kPa or less.

A25. The injectable composition of examples A24, wherein the injectablecomposition is capable of being substantially cured and thesubstantially cured composition has a modulus of elasticity of about 0.1to about 4 kPa.

A26. The injectable composition of example A24 or A25, wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has a modulus of elasticity of about 0.1to about 2 KPa.

A27. The injectable composition of one or more of examples A24 to A26,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has a modulus ofelasticity of at least 0.1 kPa.

A28. The injectable composition of one or more of examples A 19 to A27,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has a dioptric range ofaccommodation of 0 D to 10 D.

A29. The injectable composition of example A28, wherein the injectablecomposition is capable of being substantially cured and thesubstantially cured composition has a dioptric range of accommodation ofabout 0 D to about 6 D.

A30. The injectable composition of example A28 or A29, wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has a dioptric range of accommodation ofabout 0 D to about 4 D.

A31. The injectable composition of one or more of examples A19 to A30,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has extractables less thanabout 20%.

A32. The injectable composition of one or more of example A31, whereinthe injectable composition is capable of being substantially cured andthe substantially cured composition has extractables of about 0.5% toabout 18%.

A33. The injectable composition of examples A31 or A32, wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has extractables of about 0.5% to about16%.

A34. The injectable composition of one or more of examples A31 to A33,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has extractables of about0.5% to about 10%.

A35. The injectable composition of one or more of examples A31 to A34,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has extractables of about1% to about 5%.

A36. A method of making an injectable composition for forming anaccommodating intraocular lens in situ, comprising the step of mixingtogether

-   -   an organosilicon compound and    -   a hydrolytically sensitive siloxane moiety    -   wherein the mixing together is performed using catalytic        hydrosilation or condensation to form the injectable        composition.

A37. The method of example A36, wherein the organosilicon compoundcomprises linear polysiloxane polymer chains, linear poly siloxanecopolymer chains, branched polysiloxane polymer chains, or combinationsthereof.

A38. The method of example A36, wherein the wherein the hydrolyticallysensitive siloxane moiety comprises one or more of silane ether groupsand/or one of more groups of silane ester groups.

A39. The method of example A36, wherein the catalytic hydrosilylation isperformed with one or more of catalysts comprising chloroplatinic acid,Karstedt's catalyst, Palladium acetate and Platinum oxide.

A40. The method of example A36, wherein the condensation is performedwith a polyfunction silyl ester and/or silyl ether monomers.

A41. An intraocular lens formed in situ by the steps comprising:

-   -   a) injecting a composition comprising an organosilicon compound        and a hydrolytically sensitive siloxane moiety into a capsule        and    -   b) allowing the composition to cure upon contact with moisture,        water or an aqueous medium to form the intraocular lens.

A42. The intraocular lens of example A41, wherein the organosiliconcompound comprises linear polydimethylsiloxane polymer chains, linearpoly siloxane copolymer chains, branched polysiloxane polymer chains, orcombinations thereof

A43. The intraocular lens of examples A41 or A42, wherein theintraocular lens is suitably transparent.

A44. The intraocular lens of examples A41 to A43, wherein theintraocular lens has a refractive index in the range of about 1.4 to1.5.

A45. The intraocular lens of example A44, wherein the intraocular lenshas a refractive index in the range of 1.41 to 1.45.

A46. The intraocular lens of examples A44 or A45, wherein theintraocular lens has a refractive index in the range of about 1.42 to1.44.

A47. The intraocular lens of examples A41 to A46, wherein theintraocular lens has a modulus of elasticity of about 6 kPa or less.

A48. The intraocular lens of example A47, wherein the intraocular lenshas a modulus of elasticity of about 0.1 to 4 kPa.

A49. The intraocular lens of examples A47 or A48, wherein theintraocular lens has a modulus of elasticity of about 0.1 to 2 kPa.

A50. The intraocular lens of examples A41 to A49, wherein theintraocular lens has a dioptric range of accommodation of up to 10 D.

A51. The intraocular lens of example A50, wherein the intraocular lenshas a dioptric range of accommodation of about 0 D to 6 D.

A52. The intraocular lens of examples A50 or A51, wherein theintraocular lens has a dioptric range of accommodation of about 0 D to 4D.

A53. The intraocular lens of examples A41 to A52, wherein thecomposition is injected using a injecting device.

A54. A method of forming an intraocular lens in situ, by the stepscomprising:

-   -   a) injecting a composition comprising an organosilicon compound        and a hydrolytically sensitive siloxane moiety into a capsule        and    -   b) allowing the composition to substantially cure upon contact        with moisture, water or an aqueous medium to form the        intraocular lens.

A55. A method according to example A54, wherein the composition isinjected using an injection device.

A56. A method according to example A54, wherein the composition issubstantially cured to form the intraocular lens from within about 30minutes to 7 days.

A57. A method according to examples A54 to A56, wherein the intraocularlens has a modulus of elasticity of about 6 kPa or less.

A58. A method according to example A57, wherein the intraocular lens hasa modulus of elasticity of about 0.1 to 4 kPa.

A59. A method according to examples A57 or A58, wherein the intraocularlens has a modulus of elasticity of about 0.1 to 2 kPa.

A60. A method according to examples A54 to A59, wherein the intraocularlens has a refractive index in the range of about 1.4 to 1.5.

A61. A method according to example A60, wherein the intraocular lens hasa refractive index in the range of 1.41 to 1.45.

A62. A method according to examples A60 or A61, wherein the intraocularlens has a refractive index in the range of about 1.42 to 1.44.

A63. A method according to examples A54 to A62, wherein the intraocularlens has a dioptric range of accommodation of 0 D to 10 D.

A64. A method according to example A63, wherein the intraocular lens hasa dioptric range of accommodation of about 0 D to 6 D.

A65. A method according to examples A63 or A64, wherein the intraocularlens has a dioptric range of accommodation of about 0 D to 4 D.

A66 A kit comprising one or more of

-   -   an injectable composition comprising an organosilicon compound        and a hydrolytically sensitive siloxane moiety and having a        specific gravity greater than 0.95, a number average molecular        weight (M_(n)) greater than about 5,000 and a weight average        molecular weight (M_(w)) greater than about 20,000;    -   an injection device; or    -   a valve device for sealing the aperture on the surface of the        capsular bag of the eye.

A67. An accommodating intraocular lens formed in situ in the capsule bymoisture cure of an organosilicon compound and a hydrolyticallysensitive siloxane moiety and having one or more properties comprising:

-   -   i) an elastic modulus of about 6 kPa or less;    -   ii) less than about 20% of post-cure extractables;    -   iii) a refractive index in the range of about 1.4 to about 1.5;        or    -   iv) a dioptric range of accommodation of 0 to 10 D.

A68. The intraocular lens of example A67, wherein at least 50% of thepost-cure extractables have a number average molecular weight (M_(n)) ofgreater than about 30,000.

1. An injectable composition for forming an accommodating intraocularlens in situ in a capsule, comprising an organosilicon compound and ahydrolytically sensitive siloxane moiety wherein the injectablecomposition has a specific gravity greater than about 0.95, a numberaverage molecular weight (M_(n)) greater than about 5,000, a weightaverage molecular weight (M_(w)) greater than about 20,000 and iscapable of being substantially cured in situ upon contact with moisture.2. The injectable composition of claim 1, wherein the organosiliconcompound comprises linear polysiloxane polymer chains, linear polysiloxane copolymer chains, branched polysiloxane polymer chains, orcombinations thereof.
 3. The injectable composition of claim 1, whereinthe injectable composition has a specific gravity in the range of 1 to1.04.
 4. The injectable composition of claim 1, wherein thehydrolytically sensitive siloxane moiety comprises one or more of silaneether groups and/or one of more groups of silane ester groups.
 5. Theinjectable composition of claim 1, wherein the number average molecularweight (M_(n)) is in the range of about 5,000 to 150,000.
 6. Theinjectable composition of claim 1, wherein the weight average molecularweight (M_(w)) is in the range of about 20,000 to 300,000.
 7. Theinjectable composition of claim 1, wherein the injectable compositionhas mole fractions of the end groups that possess a hydrolysable moietyand cross linkable moiety in the range of greater than about 20%.
 8. Theinjectable composition of claim 1, wherein the injectable composition issubstantially cured through condensation of one or more reactive silanolgroups.
 9. The injectable composition of claim 1, wherein the injectablecomposition is capable of being substantially cured and thesubstantially cured composition has a refractive index in the range ofabout 1.41 to about 1.45.
 10. The injectable composition of claim 1,wherein the injectable composition is capable of being substantiallycured and the substantially cured composition has a refractive index ofat least 1.4.
 11. The injectable composition of claim 1, wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has a modulus of elasticity of about 0.1to about 4 kPa.
 12. The injectable composition of claim 1, wherein theinjectable composition is capable of being substantially cured and thesubstantially cured composition has a dioptric range of accommodation of0 D to 10 D.
 13. A method of making an injectable composition forforming an accommodating intraocular lens in situ, comprising the stepof mixing together an organosilicon compound and a hydrolyticallysensitive siloxane moiety wherein the mixing together is performed usingcatalytic hydrosilation or condensation to form the injectablecomposition.
 14. An intraocular lens formed in situ by the stepscomprising: a) injecting a composition comprising an organosiliconcompound and a hydrolytically sensitive siloxane moiety into a capsuleand b) allowing the composition to cure upon contact with moisture,water or an aqueous medium to form the intraocular lens. 15-19.(canceled)